The nephritic factor (NeF) of the alternative pathway of complement has been found in the sera of patients with membranoproliferative glomerulonephritis (MPGN) and partial lipodystrophy and has been described as a factor which is able to induce cleavage of the third component of complement (C3) in normal human serum through the alternative pathway. It has been demonstrated that NeF binds to and stabilizes C3bBb (alternative C3 convertase). NeF appears to be antigenically and structurally similar to IgG and therefore it might be an autoantibody directed against C3bBb complex. The relation between the development of renal lesions and the NeF mediated persistent hypocomplementemia remains unexplained. B lymphocytes from patients with MPGN were used to establish cell lines secreting NeF of either IgG or IgM classes. Sera of patients with MPGN were found contain anti- idiotypic antibodies to NeF. We isolated 3 different anti-idiotypic antibodies and found that monoclonal and several polyclonal NeF share at least one idiotope. To verify this observation we are in the process of repeating these experiments using hetero-anti-idiotypic antibodies. Nucleotide sequencing of different NeF will answer the question whether NeF are direct products of germline genes or have undergone mutations as a result of antigenic stimulation.